Recent work implicates the subfornical organ (SFO) and organum vasculosum of the lamina terminalis (OVLT), two circumventricular organs of the brain, in the behavioral and physiological controls of body water balance. The SFO and OVLT have efferent neural connections which are appropriate for the defense of water balance behaviorally and physiologically. The major objective of the proposed research is to examine the neural circuitry of water homeostatic mechanisms and distinguish the components which mediate behavioral controls and physiological controls and those that subserve both. Behaviorally, elements of the neural circuitry will be examined by making microlesions or knifecuts of its components and evaluating the preparations for deficits in drinking behavior to thirst challenges. Quantitative cerebral blood flow studies (14C-iodoantipyrine) of the same circuitry will be done to evaluate the vasomotor hypothesis for the drinking response to angiotensin. Quantitative 14C-deoxyglucose functional maping of the brain will be done under a variety of thirst challenging situations to assess the functional status of the SFO, OVLT, medial preoptic area and their circuitry as well as to locate unexpected functional connectivity in mediating responses to body water disturbances. Neuroanatomically a study of the connectivity of the SFO and OVLT will be continued to more completely describe their efferent projections and afferent sources using anterograde autoradiography and retrograde (horseradish peroxidase) tracing techniques. This additional circuitry will be studied behaviorally and functionally as described above. This work will further our understanding of the neuropsychological mechanisms for producing behavior and will provide insight into diseases related to disturbed thirst such as psychogenic polydipsia.